The Angiogenic Factor PlGF Mediates a Neuroimmune Interaction in the Spleen to Allow the Onset of Hypertension

被引：134

作者：

Carnevale, Daniela ^{[1
,2
]}

Pallante, Fabio ^{[1
]}

Fardella, Valentina ^{[1
]}

Fardella, Stefania ^{[1
]}

Iacobucci, Roberta ^{[1
]}

Federici, Massimo ^{[3
]}

Cifelli, Giuseppe ^{[1
]}

De Lucia, Massimiliano ^{[1
]}

Lembo, Giuseppe ^{[1
,2
]}

机构：

[1] IRCCS Neuromed, Dept Angiocardioneurol & Translat Med, Neuro & Cardiovasc Pathophysiol Res Unit, I-86077 Pozzilli, Italy

[2] Univ Roma La Sapienza, Dept Mol Med, I-00161 Rome, Italy

[3] Univ Roma Tor Vergata, Dept Syst Med, I-00133 Rome, Italy

来源：

IMMUNITY | 2014年 / 41卷 / 05期

关键词：

PLACENTAL GROWTH-FACTOR; II-INDUCED HYPERTENSION; REGULATE BLOOD-PRESSURE; T-CELL COSTIMULATION; TISSUE INHIBITOR; VASCULAR INFLAMMATION; CARDIAC INFLAMMATION; SALT HYPERTENSION; ANGIOTENSIN; ATHEROSCLEROSIS;

D O I：

10.1016/j.immuni.2014.11.002

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Hypertension is a health problem affecting over 1 billion people worldwide. How the immune system gets activated under hypertensive stimuli to contribute to blood pressure elevation is a fascinating enigma. Here we showed a splenic role for placental growth factor (PlGF), which accounts for the onset of hypertension, through immune system modulation. PlGF repressed the expression of the protein Timp3 (tissue inhibitor of metalloproteinases 3), through the transcriptional Sirt1-p53 axis. Timp3 repression allowed costimulation of T cells and their deployment toward classical organs involved in hypertension. We showed that the spleen is an essential organ for the development of hypertension through a noradrenergic drive mediated by the celiac ganglion efferent. Overall, we demonstrate that PlGF mediates the neuroimmune interaction in the spleen, organizing a unique and nonredundant response that allows the onset of hypertension.

引用

页码：737 / 752

页数：16

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